Marjan Azin , Kenneth H. Ngo , Jennet Hojanazarova , Shadmehr Demehri
{"title":"Topical Calcipotriol Plus Imiquimod Immunotherapy for Nonkeratinocyte Skin Cancers","authors":"Marjan Azin , Kenneth H. Ngo , Jennet Hojanazarova , Shadmehr Demehri","doi":"10.1016/j.xjidi.2023.100221","DOIUrl":"10.1016/j.xjidi.2023.100221","url":null,"abstract":"<div><p>Nonkeratinocyte cutaneous malignancies, including breast cancer cutaneous metastasis and melanoma in situ, are often poor surgical candidates. Imiquimod (IMQ), a toll-like receptor 7 agonist that activates innate immunity in the skin, is used to treat these cutaneous malignancies. However, IMQ's modest effect on the activation of adaptive immunity limits its efficacy as a monotherapy. In this study, we demonstrate that topical TSLP cytokine inducers—calcipotriol and retinoic acid—synergize with IMQ to activate CD4<sup>+</sup> T-cell immunity against nonkeratinocyte cutaneous malignancies. Topical calcipotriol plus IMQ treatment reduced breast tumor growth compared with calcipotriol or IMQ alone (<em>P</em> < 0.0001). Calcipotriol plus IMQ–mediated tumor suppression was associated with significant infiltration of CD4<sup>+</sup> effector T cells in the tumor microenvironment. Notably, topical calcipotriol plus IMQ immunotherapy enabled immune checkpoint blockade therapy to effectively control immunologically cold breast tumors, which was associated with induction of CD4<sup>+</sup> T-cell immunity. Topical treatment with calcipotriol plus IMQ and retinoic acid plus IMQ also blocked subcutaneous melanoma growth. These findings highlight the synergistic effect of topical TSLP induction in combination with innate immune cell activation as an effective immunotherapy for malignancies affecting the skin.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"3 6","pages":"Article 100221"},"PeriodicalIF":0.0,"publicationDate":"2023-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9e/73/main.PMC10507651.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41169296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"M1/M2 Macrophage Skewing is Related to Reduction in Types I, V, and VI Collagens with Aging in Sun-Exposed Human Skin","authors":"Satoshi Horiba , Munetaka Kawamoto , Ryozo Tobita , Ryota Kami , Yuki Ogura , Junichi Hosoi","doi":"10.1016/j.xjidi.2023.100222","DOIUrl":"10.1016/j.xjidi.2023.100222","url":null,"abstract":"<div><p>Sun-exposed, aged human skin is fragile because of collagen fragmentation and loss. We recently reported that the balance of M1 and M2 macrophages is associated with chronic inflammation and related inflammaging in sun-exposed human skin. In this study, we analyzed its role in the maintenance of collagen matrix formation by performing histological analyses of human facial skin. In addition, RNA sequencing, protein assays, and functional assays revealed the details of the mechanism. The number of M2 macrophages was positively correlated with the abundance of type I collagen, whereas the M1/M2 ratio was negatively correlated with the abundance of type V and VI collagen, which are the essential minor collagens required for collagen assembly in the skin; however, there was no correlation with type III collagen. Furthermore, M2 macrophages induced the expression of the proteins required for the assembly of collagen fibrils, suggesting that the M1/M2 balance controls not only the quantity but also the quality of the collagen matrix. Indeed, M1 macrophages induced abnormal collagen fibrils consisting of types I, V, and VI collagens. Our results demonstrate the relationship between the M1/M2 balance and the dysregulation of collagen homeostasis in photoaged skin and suggest the possible involvement of macrophages in skin photoaging.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"3 6","pages":"Article 100222"},"PeriodicalIF":0.0,"publicationDate":"2023-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/09/1d/main.PMC10542643.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41164216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
T. Douki, S. Caillat, D. Bacqueville, C. Géniès, C. Huyghe, H. Duplan, J. Le Digabel, C. Lauze, J. Filiol, R. Marinescu, K. Bouyer, E. Questel, G. Josse
{"title":"Nuclear and urinary measurements show the efficacy of a SPF50+ sunscreen against DNA photoproducts upon “real-life” recreational exposure","authors":"T. Douki, S. Caillat, D. Bacqueville, C. Géniès, C. Huyghe, H. Duplan, J. Le Digabel, C. Lauze, J. Filiol, R. Marinescu, K. Bouyer, E. Questel, G. Josse","doi":"10.1016/j.xjidi.2023.100227","DOIUrl":"https://doi.org/10.1016/j.xjidi.2023.100227","url":null,"abstract":"","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46775608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Taig Mac Carthy , Ignacio Hernández Montilla , Andy Aguilar , Rubén García Castro , Ana María González Pérez , Alejandro Vilas Sueiro , Laura Vergara de la Campa , Fernando Alfageme , Alfonso Medela
{"title":"Automatic Urticaria Activity Score: Deep Learning–Based Automatic Hive Counting for Urticaria Severity Assessment","authors":"Taig Mac Carthy , Ignacio Hernández Montilla , Andy Aguilar , Rubén García Castro , Ana María González Pérez , Alejandro Vilas Sueiro , Laura Vergara de la Campa , Fernando Alfageme , Alfonso Medela","doi":"10.1016/j.xjidi.2023.100218","DOIUrl":"10.1016/j.xjidi.2023.100218","url":null,"abstract":"<div><p>Chronic urticaria is a chronic skin disease that affects up to 1% of the general population worldwide, with chronic spontaneous urticaria accounting for more than two-thirds of all chronic urticaria cases. The Urticaria Activity Score (UAS) is a dynamic severity assessment tool that can be incorporated into daily clinical practice, as well as clinical trials for treatments. The UAS helps in measuring disease severity and guiding the therapeutic strategy. However, UAS assessment is a time-consuming and manual process, with high interobserver variability and high dependence on the observer. To tackle this issue, we introduce Automatic UAS, an automatic equivalent of UAS that deploys a deep learning, lesion-detecting model called Legit.Health-UAS-HiveNet. Our results show that our model assesses the severity of chronic urticaria cases with a performance comparable to that of expert physicians. Furthermore, the model can be implemented into CADx systems to support doctors in their clinical practice and act as a new end point in clinical trials. This proves the usefulness of artificial intelligence in the practice of evidence-based medicine; models trained on the consensus of large clinical boards have the potential of empowering clinicians in their daily practice and replacing current standard clinical end points in clinical trials.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 1","pages":"Article 100218"},"PeriodicalIF":0.0,"publicationDate":"2023-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026723000437/pdfft?md5=4ca1bf4ece66885ed9f24601c8bff3c1&pid=1-s2.0-S2667026723000437-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44933558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jungsoo Chang , Beverly Yu , W. Mark Saltzman , Michael Girardi
{"title":"Nanoparticles as a Therapeutic Delivery System for Skin Cancer Prevention and Treatment","authors":"Jungsoo Chang , Beverly Yu , W. Mark Saltzman , Michael Girardi","doi":"10.1016/j.xjidi.2023.100197","DOIUrl":"10.1016/j.xjidi.2023.100197","url":null,"abstract":"<div><p>The use of nanoparticles (NPs) as a therapeutic delivery system has expanded markedly over the past decade, particularly regarding applications targeting the skin. The delivery of NP-based therapeutics to the skin requires special consideration owing to its role as both a physical and immunologic barrier, and specific technologies must not only take into consideration the target but also the pathway of delivery. The unique challenge this poses has been met with the development of a wide panel of NP-based technologies meant to precisely address these considerations. In this review article, we describe the application of NP-based technologies for drug delivery targeting the skin, summarize the types of NPs, and discuss the current landscape of NPs for skin cancer prevention and skin cancer treatment as well as future directions within these applications.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"3 4","pages":"Article 100197"},"PeriodicalIF":0.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c1/fe/main.PMC10186617.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9550603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zachary A. Bordeaux , Justin Choi , Gabriella Braun , Cole Davis , Melika Marani , Kevin Lee , Christeen Samuel , Jackson Adams , Reed Windom , Anthony Pollizzi , Anusha Kambala , Hannah Cornman , Sriya V. Reddy , Weiying Lu , Olusola O. Oladipo , Martin P. Alphonse , Cameron E. West , Shawn G. Kwatra , Madan M. Kwatra
{"title":"Topical GZ21T Inhibits the Growth of Actinic Keratoses in a UVB-Induced Model of Skin Carcinogenesis","authors":"Zachary A. Bordeaux , Justin Choi , Gabriella Braun , Cole Davis , Melika Marani , Kevin Lee , Christeen Samuel , Jackson Adams , Reed Windom , Anthony Pollizzi , Anusha Kambala , Hannah Cornman , Sriya V. Reddy , Weiying Lu , Olusola O. Oladipo , Martin P. Alphonse , Cameron E. West , Shawn G. Kwatra , Madan M. Kwatra","doi":"10.1016/j.xjidi.2023.100206","DOIUrl":"10.1016/j.xjidi.2023.100206","url":null,"abstract":"<div><p>Actinic keratoses (AKs) are premalignant intraepidermal neoplasms that occur as a result of cumulative sun damage. AKs commonly relapse, and up to 16% undergo malignant transformation into cutaneous squamous cell carcinoma. There is a need for novel therapies that reduce the quantity and surface area of AKs as well as prevent malignant transformation to cutaneous squamous cell carcinomas. We recently showed that GZ17-6.02, an anticancer agent composed of curcumin, haramine, and isovanillin, inhibited the growth of H297.T cells. This study evaluated the efficacy of a topical formulation of GZ17-6.02, known as GZ21T, in a murine model of AK generated by exposing SKH1 mice to UVR<em>.</em> Treatment of mice with topical GZ21T inhibited the growth of AKs by decreasing both lesion count (<em>P</em> = 0.012) and surface area occupied by tumor (<em>P</em> = 0.002). GZ21T also suppressed the progression of AKs to cutaneous squamous cell carcinoma by decreasing the count (<em>P</em> = 0.047) and surface area (<em>P</em> = 0.049) of lesions more likely to represent cutaneous squamous cell carcinoma. RNA sequencing and proteomic analyses revealed that GZ21T suppressed several pathways, including MAPK (<em>P</em> = 0.025), phosphoinositide 3-kinase–protein kinase B (<em>P</em> = 0.04), HIF-1α (<em>P</em> = 0.016), Wnt (<em>P</em> = 0.025), insulin (<em>P</em> = 0.018), and ERBB (<em>P</em> = 0.016) signaling. GZ21T also upregulated the autophagy-promoting protein AMPK while suppressing proteins such as PD-L1, glutaminase, pAkt1 S473, and eEF2K.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"3 4","pages":"Article 100206"},"PeriodicalIF":0.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c3/c2/main.PMC10392087.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9923876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Transcriptome Profiling of Anhidrotic Eccrine Sweat Glands Reveals that Olfactory Receptors on Eccrine Sweat Glands Regulate Perspiration in a Ligand-Dependent Manner","authors":"Naoya Murayama , Takafumi Miyaki , Daisuke Okuzaki , Yasuaki Shibata , Takehiko Koji , Asuka Inoue , Junken Aoki , Hideki Hayashi , Yoshimasa Tanaka , Hiroyuki Murota","doi":"10.1016/j.xjidi.2023.100196","DOIUrl":"10.1016/j.xjidi.2023.100196","url":null,"abstract":"<div><p>Sweat maintains systemic homeostasis in humans. Although sweating disorders may cause multifaceted health problems, therapeutic options for sweat disorders have not yet been established. To gain new insight into the mechanism underlying the regulation of perspiration, we compared eccrine sweat gland transcriptomes from hidrotic and anhidrotic lesions from patients with anhidrosis and found out that olfactory receptors were expressed differentially in anhidrotic and hidrotic eccrine sweat glands. We then confirmed OR51A7 and OR51E2 expression in human eccrine sweat glands by in situ hybridization and immunohistochemistry. An alkaline phosphatase−TGFα shedding assay revealed that β-ionone activates G-proteins through OR51A7 or OR51E2. The effect of topically applied β-ionone on sweating was examined with the quantitative sudomotor axon reflex test, which showed that responses to β-ionone differed between sexes. Topical β-ionone attenuated female sweating and augmented male sweating. Taken together, this study suggests that olfactory receptors expressed in eccrine sweat glands may regulate sweating in response to odorous ligands on the basis of sex. These unexpected results indicate that olfactory receptors may modulate sweating and that olfactory receptor modulators may contribute to the management of sweat disorders.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"3 4","pages":"Article 100196"},"PeriodicalIF":0.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/87/d8/main.PMC10392076.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9929845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Beatrix D.G. Evers , Miriam Hils , Christoph Heuser , Inga M. Hölge , Désirée Argiriu , Yuliya Skabytska , Susanne Kaesler , Christian Posch , Percy A. Knolle , Tilo Biedermann
{"title":"Inflammatory Cues Direct Skin-Resident Type 1 Innate Lymphoid Cells to Adopt a Psoriasis-Promoting Identity","authors":"Beatrix D.G. Evers , Miriam Hils , Christoph Heuser , Inga M. Hölge , Désirée Argiriu , Yuliya Skabytska , Susanne Kaesler , Christian Posch , Percy A. Knolle , Tilo Biedermann","doi":"10.1016/j.xjidi.2023.100204","DOIUrl":"10.1016/j.xjidi.2023.100204","url":null,"abstract":"<div><p>Innate lymphoid cells (ILCs) are gatekeepers in barrier organs, where they maintain tissue integrity and contribute to host defense as well as tissue repair. Inappropriate activation of ILCs, however, can lead to immunopathology with detrimental results. In this study, we focused on type 1 ILCs (ILC1s), which under inflammatory conditions constitute a poorly defined population with ambiguous functions. To delineate the properties of ILC1s in skin pathology, we used the well-established mouse model of imiquimod-induced psoriasis. Although ILC1s represented a minority among cutaneous lymphocytes in vehicle-treated controls, they rapidly expanded during early psoriasis and ultimately increased by >20-fold. This rapid increase was verified using two additional psoriasis models. Inflammatory ILC1s from imiquimod-treated skin were defined as CD44<sup>+</sup>, CXCR6<sup>+</sup>, and CD11b<sup>+</sup> and substantially contributed to TNF-α and GM-CSF production, rendering them a potential candidate to shape the inflammatory infiltrate. In accordance with the psoriasis-specific microenvironment, skin ILC1s upregulated the IL-23 receptor whereas expression of the IL-12Rβ2 subunit was diminished. As a consequence, neutralization of IL-12 only had a minor impact, whereas blocking IL-23 reduced both ILC1 abundance and disease severity. Together, our findings identify skin ILC1s as a likely player in early psoriasis and a prospective target for therapeutic approaches.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"3 4","pages":"Article 100204"},"PeriodicalIF":0.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6b/01/main.PMC10392090.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9932972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiuju Dai , Ken Shiraishi , Jun Muto , Hideki Mori , Masamoto Murakami , Koji Sayama
{"title":"Nuclear IL-33 Plays an Important Role in EGFR-Mediated Keratinocyte Migration by Regulating the Activation of Signal Transducer and Activator of Transcription 3 and NF-κB","authors":"Xiuju Dai , Ken Shiraishi , Jun Muto , Hideki Mori , Masamoto Murakami , Koji Sayama","doi":"10.1016/j.xjidi.2023.100205","DOIUrl":"10.1016/j.xjidi.2023.100205","url":null,"abstract":"<div><p>Nuclear IL-33 levels are high at the epidermal edges of skin wounds and facilitate wound healing. However, IL-33−mediated regulation of keratinocyte (KC) biology during wound healing remains poorly understood. During skin-wound healing, KC migration and re-epithelialization are mediated predominantly by EGFR signaling activation and depend on the function of signal transducer and activator of transcription 3 (STAT3). We found that migrating KCs at the leading edges of mouse skin wounds exhibited concomitant induction and nuclear colocalization of IL-33 and phosphorylated STAT3. In cultured human KCs, activation of EGFR signaling caused rapid elevation of nuclear IL-33, which directly interacts with phosphorylated STAT3, promoting STAT3 activation. In vitro KC migration and wound-healing assays revealed that high nuclear IL-33 levels were required for KC migration and wound closure. KC mobility associated with a lack of suprabasal epidermal keratins and extracellular matrix degradation mediated by matrix metalloproteinases (MMPs) control cell migration at the intracellular and extracellular levels, respectively. In EGFR-activated KCs, nuclear IL-33 mediated keratin 1 and 10 downregulation and MMP9 upregulation by promoting STAT3 activation and limited MMP1, MMP3, and MMP10 induction by suppressing NF-κB transactivation. Thus, epidermal nuclear IL-33 is involved in KC migration and wound closure by regulating the STAT3 and NF-κB pathways.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"3 4","pages":"Article 100205"},"PeriodicalIF":0.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/19/94/main.PMC10333683.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10174860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Markqayne Ray , Kavita Gandhi , Keshia Maughn , Amit G. Pandya
{"title":"Diagnosed Prevalence and Incidence of Vitiligo in the United States: Analysis of Employer-Sponsored Insurance Claims","authors":"Markqayne Ray , Kavita Gandhi , Keshia Maughn , Amit G. Pandya","doi":"10.1016/j.xjidi.2023.100199","DOIUrl":"10.1016/j.xjidi.2023.100199","url":null,"abstract":"","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"3 4","pages":"Article 100199"},"PeriodicalIF":0.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9c/b0/main.PMC10186599.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9499269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}